Summary of Work: The primary objective of this study is to examine the association between insulin-like growth factor (IGF)-I and two of its binding proteins (IGFBP-4 and IGFBP-5) and bone density of the hip and spine in 100 men and 100 women ages 60 and older from Cycle 6 of the Framingham Offspring Study Osteoporosis Call-back Study. The main hypotheses to be investigated are: 1. IGF-I has a modest direct association with bone mineral density (BMD)f the hip and spine; however, 2. IGFBP-4, which inhibits IGF action, is strongly and inversely correlated with BMD. 3. IGFBP-5, which potentiates IGF-induced bone cell proliferation, is positively correlated with BMD. 4. IGFBP-4 is strongly and positively associated with parathyroid hormone (PTH). Since calcium deficiency is associated with secondary hyperparathyroidism, IGFBP-4 will be increased in calcium deficient women. Assays for PTH and IGFBP-I also will be included, extending the usefulness of these data for investigating the mechanisms underlying age-related changes in bone as well their role in the development of other health conditions in old age. Data have been collected and are being analyzed.